The techniques of nuclear magnetic resonance are well known to the art. In general, nuclear magnetic resonance involves aligning the magnetic moments of atomic nuclei in a sample by exposing the sample to an external magnetic field. A pulse of radio frequency energy is then applied to the sample, to cause the moments of the nuclei to be aligned along a particular axis, typically 90.degree. to the axis of the external magnetic field. Over time, the nuclei will return to alignment with the external field. As they do so, they emit electromagnetic radiation which can be detected. The rate at which the moments of the nuclei return to alignment with the external field is characteristic of the nuclei and the nuclear site. This fact is used in a variety of methods for generating images of the density of the nuclei, for example, in a "slice" of a human body or other sample in which they are located. In this way, a detailed cross-sectional view of the body is provided, in a non-invasive technique.
A number of different types of NMR-produced images are available, in which the intensity of each element of the image varies with a different parameter. Tissue type is perhaps the most usual. Images in which the intensity of each element varies with blood flow rate have also been provided, as discussed below.
One image which is not presently available on commercial NMR imagers used clinically is one in which the intensity of the elements of the image is proportional to flow at very low rates, specifically the rate of blood flow in capillaries of organs. This would be of great relevance in determination of the health of organs, and also to determine whether adequate blood is being supplied to them.
The use of nuclear magnetic resonance for measurement of flow of liquids is well known in the art, and several different techniques have been proposed. Moore et al., U.S. Pat. No. 4,015,196, suggests the application of a technique known as steady state free precession to the study of flow. The steady state free precession technique is defined generally at column 7, lines 15-57, of the Moore et al. patent and is related to flow among other uses at column 7, lines 58-61.
However, for a variety of reasons, the early SSFP techniques became unpopular in the art. One reason is that newly introduced spin-echo methods gave superior gray/white matter contrast in brain images. Another reason has to do with the recording of the NMR signal itself. In early SSFP techniques, the magnetization only rephased at the time radio frequency energy was being transmitted to the sample. Because the transmission of energy interferes with the reception of the very small NMR signal, some of the signal during the time of rephasing cannot be recorded. Recently, two and three dimensional Fourier techniques for SSFP have been developed and tissue contrast has improved (see, for example, Hawkes & Patz, "Rapid Fourier Imaging Using SSFP"), these more recently developed Fourier techniques allow for the complete data collection of the rephasing NMR signal.
The use of magnetic field gradients with NMR has long been recognized as introducing a flow sensitivity to the received signal. The applications of spin echo techniques to flow are discussed in a number of articles. See "Nuclear Magnetic Resonance Blood Flow Measurements in the Human Brain" by Singer and Crooks, Science, Vol. 221, pp. 654-656 (1983); "NMR Diffusion and Flow Measurements: An Introduction to Spin Phase Graphing" by Singer, J. Phys. B: Scientific Instruments, Vol. 11, pp. 281-291 (1978); "The Spatial Mapping of Translationship Diffusion Coefficients by the NMR Imaging Technique." Taylor and Bushell, Phys. Med. Biol., Vol. 30, No. 4, pp. 345-349 (1985); Modern Developments in Flow Measurement, Chapter 2-1: "Recent Measurements of Flow Using Nuclear Magnetic Resonance Techniques" by Singer and Grover, pp. 38-47 (1971); "Using NMR to Measure Blood Flow Volume and Velocity" by Singer and Crooks, Barrington Publications, Inc.; and U.S. Pat. No. 4,520,828 to Burl et al. All of these references, as well as the Moore et al. patent, are incorporated by reference herein.
An example of a known flow measurement technique, such as that employed by Singer and Crooks, may be described generally as follows. An initial magnetic field H.sub.0 is supplied to cause all the nuclear spins to line up. The spins are then tipped away from the H.sub.o direction by the application of an RF pulse, using what is referred to as a 90.degree. pulse, to indicate that the spins are rotated 90.degree. with respect to the applied magnetic field H.sub.0. A magnetic field having a gradient (that is, the magnetic field varies in the plane of the "slice" which is to be measured) is applied, which then causes the in-phase spins to dephase as a function of time. After a specific time .tau., a second ratio frequency pulse is applied, which again tips the spins in the slice. Nuclei of, for example, blood, which have flowed into the slice of the body during the period .tau. are tipped by application of the second radio frequency pulse, as are any which had become realigned with the external field H.sub.0 in the interval. Ordinarily, the interval .tau. will be much less than the typical relaxation time T.sub.1, such that the contribution of the latter effect is small. Accordingly, the signal detected after the application of the second pulse contains a component proportionate to blood flow, as well as a smaller component proportional to the amount of nuclei which relaxed during the time .tau..
A number of different measurements using gradually increased times .tau. are performed. At some point, a maximum signal value will be reached, indicating that all the blood in the slice has been replaced during the period .tau..
It will be appreciated by those skilled in the art that for each value of .tau., the experiment just described provides the data for a single projection of the imaged slice. A number of different projections are made for each value of .tau. in order to make an image of the material which flowed into the slice in the time .tau.. The actual number of projections made determine the resolution of the image.
As is well known, the nuclei precess about the external field at a frequency referred to as the Larmor frequency, which is proportional to the magnetic field at their location. The signal emitted is a function of the precession frequency. Since a gradient has been imposed upon the external field, the Larmor frequencies of nuclei at different positions within the slice vary. Accordingly, the Fourier transform, providing as it does a frequency distribution of the nuclei, simultaneously provides a spatial distribution or projection of the nuclear density within the matrix. Hence, the Fourier-transformed data can be used to directly form an image. This imaging technique, of course, is well known to the prior art, and is described here as an example of an imaging technique. It is referred to here only to provide a basis for the subsequent discussion.
The Singer and Crooks technique just described requires knowledge of vein volume in order to generate an actual flow rate value. This requires that the vein or artery through which flow is to be measured be large enough that it can actually be measured on the image, and a value for volume thus calculated. In practice, this means that the vein must be at least 2 or 3 millimeters in diameter. Capillary flow is therefore not measurable using this technique, because capillaries (having diameters less than 5 microns) are too small to show up individually on the image. Furthermore, the technique impliedly assumes that the flow is essentially perpendicular to the plane of the slice. Capillary flow may be thought of as a convoluted flow, and cannot be assumed to be in any given direction at any given time, such that this assumption will not hold true. Furthermore, the best result reported by Singer and Crooks is measurement of flow at a rate of about 2 centimeters per second; typical rates of capillary flow are lower by a factor of about 20. For all these reasons, the Singer and Crooks technique is not applicable to very low flow rates in very small vessels, such as capillary flow.